Clinical Information

Lupus anticoagulants (LA) are immunoglobulins (IgG, IgM, IgA, or a combination of these) of autoimmune type that are specifically directed against antigenic complexes of negatively charged phospholipids (such as phosphatidylserine or phosphatidylethanolamine) and coagulation-related proteins (such as beta-2-glycoprotein I) or clotting factors (including prothrombin [factor II] or factor X), and which cause prolongation of phospholipid-dependent clotting time tests due to inhibition.

LA are functionally and clinically distinct members of a broader group of antiphospholipid autoantibodies that includes immunologically detectable anticardiolipin antibodies or antibodies against other phospholipid-protein complexes. LA interfere with specific coagulation factor-phospholipid interactions, typically causing prolongation of 1 or more phospholipid-dependent clotting time tests (eg, activated partial thromboplastin time: APTT, dilute Russell's viper venom time: DRVVT) due to inhibition. This characteristic in vitro inhibition can be overcome by addition of excess phospholipid.

Because of the heterogeneous nature of LA antibodies, no single coagulation test can identify or exclude all LA. Currently, the International Society on Thrombosis and Haemostasis and the Clinical and Laboratory Standards Institute (CLSI) recommend testing for LA with at least 2 phospholipid-dependent clotting time assays based on different coagulation pathways and principles (eg, lupus-sensitive APTT and DRVVT).

In addition, given the potential for false-positive results in patients on anticoagulants, a profile or panel of coagulation tests is performed, including the prothrombin time (PT), APTT, thrombin time (TT), and DRVVT. If the PT, APTT, and/or DRVVT are prolonged, additional testing may include mixing tests with normal plasma (to evaluate for inhibition) and the use of excess phospholipid in appropriate assay systems to evaluate for phospholipid-dependent inhibition. Additional reflexive testing helps determine presence or absence of anticoagulants and/or inhibitors to other factors.

The diagnosis of LA requires performance and interpretation of complex coagulation testing, as well as correlation with available clinical information, including evidence of persistence of LA over time (≥12 weeks).

The venom obtained from Russell's viper (Vipera russelli) contains enzymes that directly activate coagulation factors V and X, bypassing the activation of factors VII, VIII, IX, XI, and XII, and therefore, the effect of deficiencies or inhibitors of these factors. Diluting the phospholipid necessary for the clotting factor interactions increases the sensitivity to LA and the likelihood of identifying a phospholipid-dependent inhibitor that may not be detected by other coagulation tests with a higher phospholipid content (eg, LA-insensitive APTT reagents).

The DRVVT screen ratio test is one of several available in vitro tests that may be used to screen and confirm for presence of LA or to help exclude LA. DRVVT testing is used in conjunction with other appropriate coagulation tests (reflexive testing panels) to assist in detection and confirmation of LA, or help exclude their presence.

The DRVVT may be abnormally prolonged (DRVVT screen ratio ≥1.20) by LA as well as coagulation factor deficiencies, anticoagulant effects, or other types of coagulation factor inhibitors.

Specimens with abnormal results (DRVVT screen ratio ≥1.20) are subjected to reflexive testing (see Testing Algorithm). With the reflexive testing algorithm, the sensitivity of DRVVT testing for LA diagnosis is approximately 65% to 70% and the specificity is 95% or higher.

Although LA cause prolonged clotting times in vitro, there is a strong association with thrombosis risk. However, not all patients with persisting LA develop thrombosis.